Study On The Anti-atherosclerotic Effects Of Flaxseed Oil

Atherosclerosis is the pathogenesis of cardiovascular diseases,which is the cause of death in the word.In the recent years,the morbidity of cardiovascular disease is increasing rapidly.According to the WHO report in 2010,the number of deaths caused by cardiovascular disease is up to 17.5 million people,and will be increased to 23.3million people in the year of 2030.In our country,according to the"Chinese cardiovascular disease report 2014",the incidence of cardiovascular disease continues to increase,the mortality is 42%and the patients is up to 290 million with the development of economic society and the accelerated population aging and urbanization process,?-3 fatty acids reduce the risk of the occurence of cardiovascular disease,and its biologic and molecular effect can modulate the mechanisms of development and progression of atherosclerosis,which include its effects on inflammation,platelet function,triglyceride levels,blood pressure and the stability of atherosclerotic plaques.Flaxseed oil has rich polyunsaturated fatty acids,which is the richest source of?-linolenic acid.There's studies showed that flaxseed oil and?-Linolenic acid has lipid lowering,inflammation inhibiting,anti-atherosclerosis and cardiovascular disease preventing effects,but the mechanism of it's anti-atherosclerotic effects is unknown.In this study,We aimed at the flaxseed oil and established different animal models so as to select the best one,and then studied the mechanism of it's anti-atherosclerotic effects.We mainly aimed to provide a theoretical basis for the development of high value-added functional food and healthy products.The main results are as follows:?1?The selection of animal model for atherosclerosis.In this study,We established four kinds of atherosclerotic models with SD rats and ApoE^-/-mouse so as to select the best animal model for atherosclerosis.Methods:Sixty male SD rats were randomly divided into three groups:the first group was fed on normal diets as control group;the second group was fed on high cholesterol diets as model 1 group;the third group was injected with a single dose of vitamin D₃ and fed on high fat diet,which was model 2 group.Sixty C57BL/6 male mice including 20C57 BL/6 mouse and 40 Apo E^-/-mouse which was devided into normal diet fed group as model 3 and high fat diet group as model 4.After 6 months,plasma lipids and inflammatory factors were detected,and the aorta was separated for oil red O and HE staining.Resuls:Compared with the normal group,plasma TC,IL-6 and CRP levels in model 1 and model 2 group were significantly elevated?P<0.05?.But there's no difference between the three groups in plasma TG,LDL-C and HDL-C levels?P>0.05?,and both of the two models didn't have atherosclerotic plaques and the characteristics of the early stages of atherosclerosis.In addition,compared with the normal group,plasma TC,TG,LDL-C,IL-6 and CRP levels of model 3 and model 4 were significantly elevated?P<0.05?,and were significantly higher in model 4 than model 3?P<0.05?.But plasma HDL-C levels of model 4 were significantly reduced?P<0.05?.Oil red O and HE staining showed that model 3 only had lipid deposition and small atherosclerotic plaques in aortic arch;but the model 4 had developed typical characteristics of atherosclerosis.Conclusion:Both the two models of SD rats established with high cholesterol diets and high cholesterol diets+Vitamin D₃ were not suitable for atherosclerosis research;Model 3 only had the early stage atherosclerotic characteristics;Model 4 mice had developed typical characteristics of atherosclerosis and were more suitable for atherosclerosis research.?2?The mechanism of the anti-atherosclerotic effects of flaxseed oil.Sixty 8 weeks male C57 BL/6 mouse including 20 C57 BL/6 mouse and 40 Apo E^-/-mouse which were randomly divided into three groups:the first group was the wild type mouse fed on normal diets as control group?NG?;the second group was ApoE^-/-mouse fed on high cholesterol diets?HG?;the third group was ApoE^-/-mouse fed on high cholesterol diets which were added flaxseed oil?FG?.After 12weeks,The aorta was separated for oil red O,HE and masson staining and serum lipids and inflammatory factors were detected,We also used the immunohistochemistry method to detected whether the flaxseed oil impact on the signal of TLR4-NF-?B and SCAP-SREBP-2/LDLR,and has anti-inflammatory and anti-atherosclerotic effects.Results:Oil red O,HE and masson staining showed that NG mouse didn't have lipid deposition and atherosclerotic plaques formation in the aorta,while the HG mouse had formed obvious atherosclerotic plaques and massive myofibrils and collagen fibers.Compared with the HG mouse,FG mouse atherosclerotic plaque area decreased significantly?P<0.01?,and only had a small amount of myofibrils and collagen fibers formation.Compared with the NG group,the serum level of TC,TG and LDL-C in HG and FG group were significantly increased,and the difference was statistically significant?P<0.01?.While the HDL-C was significantly reduced and the difference was statistically significant?P<0.01?.Compared with NG group,serum pro-inflammatory factor IL-6 was significantly increased.Compared with HG group,the serum level of TC,LDL-C and pro-inflammatory factor IL-6 in FG group were significantly reduced,and the level of HDL-C was significantly increased,and the difference was statistically significant?P<0.01?.In addition,even though there is sligthly increased expression of the anti-inflammatory factor IL-10 in HG group when compared with the NG group,there was not statistically significant?P>0.05?.But the expression of IL-10 in the FG group was significantly increased when compared with the two groups,and the difference was statistically significant?P<0.01?.Immunohistochemistry results showed that compared with NG,the expression of TLR4,NF-?B,SCAP,SREBP-2,LDLR and HMGCR in HG and FG group were significantly increased,and the difference was statistically significant?P<0.01?.But when compared with the HG group,the expression of these factors in FG group was significantly reduced,and the difference was statistically significant?P<0.01?.Conclusion:Flaxseed oil can significantly improve the blood lipid,and exert anti-inflammatory and anti AS effect through the mediation of TLR4-NF-kappa B and SCAP-SREBP-2/LDLR pathway.